A preclinical model to investigate normal tissue damage following fractionated radiotherapy to the head and neck

Abstract

Radiotherapy of head and neck cancer is known to cause both early and late-occurring toxicities. To better appraise normal tissue responses and their dependence on treatment parameters such as radiation field and type, as well as dose and fractionation scheme, a preclinical model with relevant endpoints is required. 12-week old female C57BL/6J mice were irradiated with 100 or 180 kV X-rays to total doses ranging from 30 to 85 Gy, given in 10 fractions over 5 days. The radiation field covered the oral cavity, swallowing structures, and salivary glands. Monte Carlo simulations were employed to estimate tissue dose distribution. The follow-up period was 35 days, in order to study the early radiation-induced effects. Baseline and post irradiation investigations included macroscopic and microscopic examinations of the skin, lips, salivary glands, and oral mucosa. Saliva sampling was performed to assess the salivary gland function following radiation exposure. A dose dependent radiation dermatitis in the skin was observed for doses above 30 Gy. Oral mucositis in the tongue appeared as ulcerations on the ventral surface of the tongue for doses of 75-85 Gy. The irradiated mice showed significantly reduced saliva production compared to controls. In summary, a preclinical model to investigate a broad panel of normal tissue responses following fractionated irradiation of the head and neck region was established. The optimal dose to study early radiation-induced effects was found to be around 75 Gy, as this was the highest tolerated dose that gave acute effects similar to what is observed in cancer patients.

TGF-β3 increases the severity of radiation-induced oral mucositis and salivary gland fibrosis in a mouse model

“…Female C57BL/6J mice were purchased from Janvier (France) at nine weeks of age and randomly assigned into three treatment groups: Treatment with TGF-β3 and fractionated RT (RT + TGF-β3) (n=10), fractionated RT only (RT reference) (n=10) and non-irradiated controls (n=10). Data for the non-irradiated controls and the RT reference group have previously been published in (Juvkam et al 2022) and (Juvkam et al 2023). A detailed description of the treatment setup is available in (Juvkam et al 2022).…”

“…It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted September 15, 2023. ; https://doi.org/10.1101/2023.09.12.557315 doi: bioRxiv preprint fractionated RT only (RT reference) (n=10) and non-irradiated controls (n=10). Data for the non-irradiated controls and the RT reference group have previously been published in (Juvkam et al 2022) and (Juvkam et al 2023). A detailed description of the treatment setup is available in (Juvkam et al 2022).…”